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'Revertant' DCIS in human axillary breast carcinoma metastases
S H Barsky1, S A Doberneck, M D Sternlicht
1Department of Pathology, UCLA School of Medicine 90024, USA.
The Journal of Pathology
|December 9, 1997
Summary
Metastatic breast cancer can revert to a non-invasive ductal carcinoma in situ (DCIS) growth pattern within lymph nodes. This reversion shows distinct characteristics and may indicate epigenetic regulation of metastasis.
Area of Science:
- Oncology
- Cancer Biology
- Epigenetics
Background:
- Experimental evidence in mice suggests epigenetic regulation of metastasis with partial reversion.
- Metastatic colonies may shift from active spreading to in situ growth post-colonization.
Purpose of the Study:
- To investigate the occurrence of metastatic reversion to ductal carcinoma in situ (DCIS) in human breast cancer.
- To characterize the histological and molecular features of revertant DCIS in nodal metastases.
Main Methods:
- Review of 200 cases of metastatic human breast cancer.
- Immunohistochemical analysis for basement membrane components (laminin, type IV collagen) and myoepithelial markers (maspin, S-100, smooth muscle actin).
- Digital image analysis for nuclear size and assessment of Her-2/neu, p53, Ki-67, ER, and EGFR status.
Main Results:
- A 21% incidence of reversion to DCIS pattern was observed in axillary nodal metastases.
- Revertant DCIS areas showed intact basement membranes but lacked myoepithelial cells, distinguishing them from primary DCIS.
- Histological patterns, subtypes, nuclear size, and molecular markers (Her-2/neu, p53, Ki-67) of revertant DCIS were highly concordant with primary DCIS.
- Revertant DCIS cases were associated with ER-negative/EGFR-positive status and significantly higher nodal involvement.
Conclusions:
- The findings suggest that reversion of the metastatic phenotype occurs in human breast cancer, specifically to a DCIS-like state within metastases.
- This reversion phenomenon may be epigenetically regulated, mirroring observations in experimental models.
- The presence of revertant DCIS is linked to more extensive nodal disease and specific receptor expression patterns.